The objective is to identify deficient structure and function within brain areas, which control breathing and blood pressure in early life, and thus assist determination of failure mechanisms in the Sudden Infant Death Syndrome (SIDS). Brain structures identified as showing neuroanatomic and functional neural deficits in a condition characterized by failure to breathe during sleep and deficient blood pressure control, Congenital Central Hypoventilation Syndrome (CCHS), will be evaluated for defects in axonal integrity and ability of selected areas to respond with appropriate timing to autonomic and ventilatory challenges. The brain areas selected for study showed circumscribed anatomical deficits in cerebellar structures and regions encompassing fiber bundles interconnecting limbic structures; these areas mediate the perception of air hunger, regulation of blood pressure lowering or elevation, and detection of CO2 and hypoxia. We will use diffusion tensor imaging to evaluate axonal integrity and distribution within areas which showed cellular or axonal damage in the syndrome, including fibers 1) of the cingulum bundle, 2) extending caudally from the caudate nucleus, and ventrally to the basal forebrain, 3) projecting to the mid-hippocampus, and 4) from the inferior olive to Purkinje neurons of the cerebellar cortex and deep nuclei in 53 CCHS patients and 53 age-and gender-matched controls. We will examine timing of cerebellar, pontine, posterior thalamic and limbic responses with functional magnetic resonance imaging procedures to successive hypercapnia and Valsalva maneuvers to evaluate coordination of activity within these areas. The studies can reveal whether aberrant brain structure responses to breathing and blood pressure challenges result from nerve fiber loss, and whether deficient timing of brain structure action accompanies stimulation of chemoreceptor and blood pressure regulation sites. Since SIDS may result from hypotension or failure to enhance breathing to hypoxia, the studies may describe mechanisms of failure in the syndrome.